Shining a spotlight on the inclusion of disabled participants in clinical trials: a mixed methods study.

BACKGROUND: It is crucial to include a wide range of the population in clinical trials for the outcome to be applicable in real-world settings. Existing literature indicates that under-served groups, including disabled people, have been excluded from participating in clinical trials without justification. Exclusion from clinical trials exacerbates disparities in healthcare and diminishes the benefits for excluded populations. Therefore, this study was conducted to investigate potential obstacles that prevent disabled people from participating in clinical trials in the United Kingdom (UK). METHODS: The study was carried out through an explanatory sequential mixed methods design. The Imperial Clinical Trials Unit devised and implemented an online questionnaire-based survey (with open/closed-ended questions) and an online focus group discussion. The target population were disabled people, family members/carers of disabled people and staff involved in clinical trials, whereupon the sample was recruited by convenience sampling methods via posters and emails through various networks. The Qualtrics XM survey system was used as the host platform for the online survey, and Microsoft Teams was used for an online focus group discussion. The focus group discussion was conducted to gain a deeper understanding of the themes identified from the survey responses. We analysed responses to the survey via descriptive analysis and used thematic analysis to synthesise the free-text answers from the survey and focus group discussion. RESULTS: We received 45 responses to the survey questionnaire and 5 disabled people took part in a focus group discussion. Our findings highlighted the differences between the perspectives of researchers and those "being researched" and different types of barriers experienced by disabled people: opportunity barriers (inadequate recruitment strategy and ambiguous eligibility criteria), awareness barriers (perception of disability) and acceptance/refusal barriers (available support and adjustment, and sharing of trial results). CONCLUSION: Our findings support perspectives drawn from the Ford Framework regarding the need to consider all barriers, not just up to the point of enrolment into trials but also beyond the point of inclusion in clinical trials. We support calls for the introduction of legislation on including disabled people in clinical trials, implementation of industry/community-wide participatory approaches and the development of guidelines, a combined public-private approach.

Statistical analysis plan for the Dual mTorc Inhibition in advanCed/recurrent Epithelial ovarian, fallopian tube or primary peritoneal cancer (of clear cell, endometrioid and high-grade serous type, and carcinosarcoma) trial (DICE).

BACKGROUND: Treatment for ovarian cancer includes platinum-based chemotherapy, but many women become resistant to chemotherapy, becoming platinum-resistant. Standard of care for these women is weekly paclitaxel chemotherapy, but cancers can often become paclitaxel resistant. TAK228, an investigational dual TORC1/2 inhibitor, is an oral therapy that can be added to standard treatment. The DICE trial is a phase II international multicentre, parallel-group, superiority clinical trial with 1:1, open label randomisation which has the aim of investigating the effectiveness of TAK228 plus weekly paclitaxel. The planned sample size is 124 women (62 per treatment arm) with platinum-resistant ovarian cancer. OBJECTIVE: To outline the planned analyses for DICE in a statistical analysis plan (SAP) before database hard lock and the start of analysis. This ensures that bias is minimised during the analysis phase. RESULTS: This SAP provides detailed descriptions of the analysis principles and statistical procedures for analysing primary and secondary outcomes of the trial. The primary outcome is overall progression-free survival (PFS). Secondary outcomes include progression-free survival (PFS) at 24 weeks, overall response rate (ORR), duration of response (DoR), time to progression (TTP), clinical benefit rate (CBR) at 4 months, Cancer Antigen 125 (CA125) response according to Gynaecological Cancer Intergroup (GCIG) criteria, overall survival (OS), safety and tolerability as assessed by adverse events and the quality-of-life questionnaires (EORTC QLQ-C30 and EORTC QLQ-OV28). This detailed description includes significance levels, sensitivity analyses and compliance analysis. DISCUSSION: The DICE trial will determine whether the addition of TAK228 to weekly paclitaxel chemotherapy shows a statistically significant improvement to participant's progression free and overall survival and that the adverse events (AEs) and quality of life (QoL) are not significantly worse than the standard treatment. The study commenced recruitment in September 2018. An interim analysis was performed in early 2021, the results of which advised continuation of the trial. The study recruitment is ongoing and is due to complete by the end of 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT03648489 . Registered on 27 August 2018.